Knockdown of BCL2L12 leads to cisplatin resistance in MDA-MB-231 breast cancer cells.
BCL2L12, a newly identified member of Bcl-2 family, contains a BH2 domain and a putative BH3 domain. It was found to be highly expressed in normal breast tissues, and was associated with favorable prognosis in breast cancer patients. Here, we reported that the mRNA levels of BCL2L12 and its transcript variant BCL2L12A could be upregulated upon cisplatin treatment in MDA-MB-231 breast cancer cells. Knockdown of BCL2L12 and BCL2L12A dramatically inhibited cisplatin-induced apoptosis. In contrast, ectopic expressions of each of the proteins promoted cisplatin-induced apoptosis. These results indicated that decreased expressions or loss of BCL2L12 and BCL2L12A may contribute to the cisplatin resistance in breast cancer patients. Furthermore, we found that cisplatin-induced downregulation of beta-catenin was partially suppressed in BCL2L12- and BCL2L12A-knocked down MDA-MB-231 cells, which indicated that knockdown of these two proteins may stabilize beta-catenin in cisplatin-induced apoptosis. In short, we proposed that BCL2L12 and BCL2L12A may play an important role in cisplatin-induced apoptosis in MDA-MB-231 breast cancer cells.
Hong
Yi
Y
Gene Research Center, Institutes of Biomedical Science, Shanghai Medical College of Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Yang
Junwu
J
Wu
Weibing
W
Wang
Wenzong
W
Kong
Xiangfei
X
Wang
Yanlin
Y
Yun
Xiaojing
X
Zong
Hongliang
H
Wei
Yuanyan
Y
Zhang
Si
S
Gu
Jianxing
J
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C430100:BCL2L12 protein, human; D009124:Muscle Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D002945:Cisplatin